MYKACET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MYKACET (MYKACET).
MYKACET (acetaminophen) is a centrally acting analgesic and antipyretic. Its exact mechanism is not fully understood, but it is thought to involve inhibition of cyclooxygenase (COX) isoenzymes in the central nervous system, particularly COX-2, and modulation of descending serotonergic pathways.
| Metabolism | Acetaminophen is extensively metabolized in the liver via conjugation with glucuronic acid (glucuronidation) and sulfuric acid (sulfation). A minor metabolite (N-acetyl-p-benzoquinone imine, NAPQI) is formed via cytochrome P450 isoenzymes (CYP2E1, CYP1A2, CYP3A4) and is primarily detoxified by conjugation with glutathione. |
| Excretion | Primarily renal excretion of unchanged drug via glomerular filtration and active tubular secretion; >90% of administered dose appears in urine within 24 hours; minimal biliary/fecal elimination (<5%). |
| Half-life | Terminal elimination half-life is approximately 2-4 hours in patients with normal renal function; extended to 12-24 hours in moderate to severe renal impairment (CrCl <30 mL/min), requiring dose adjustment. |
| Protein binding | Approximately 20-30% bound to serum proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is 0.3-0.5 L/kg, indicating distribution primarily into extracellular fluid; does not extensively penetrate tissues or cross the blood-brain barrier. |
| Bioavailability | Oral bioavailability is approximately 50-70% due to first-pass metabolism; intravenous administration yields 100% bioavailability. |
| Onset of Action | Intravenous: Onset of action occurs within 30 minutes; oral: Onset within 1-2 hours. |
| Duration of Action | Duration of action is 6-8 hours for the intravenous route and 8-12 hours for the oral route, dependent on renal function and dosing interval. |
4 g intravenous every 8 hours over 3 hours, based on piperacillin 4 g and tazobactam 0.5 g.
| Dosage form | CREAM |
| Renal impairment | For CrCl 20-40 mL/min: 3 g (piperacillin 3 g / tazobactam 0.375 g) q8h; CrCl <20 mL/min: 2 g (piperacillin 2 g / tazobactam 0.25 g) q12h. |
| Liver impairment | No dose adjustment required for hepatic impairment; use standard dosing. |
| Pediatric use | For infants >2 months and children <40 kg: 100 mg/kg piperacillin component every 8 hours; for children ≥40 kg: adult dose (4 g q8h). |
| Geriatric use | Adjust dose based on renal function; no specific age-related adjustments beyond renal dosing. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MYKACET (MYKACET).
| Breastfeeding | No data on presence in human milk, effects on milk production, or nursing infant. Animal studies show drug and metabolites present in milk. Because of potential for serious adverse reactions in breastfed infants, advise women to discontinue breastfeeding during treatment and for 2 weeks after last dose. M/P ratio: unknown. |
| Teratogenic Risk | MYKACET (acalabrutinib) is a BTK inhibitor. In animal studies, embryo-fetal toxicity was observed at maternal exposures below clinical doses. In pregnant women, no adequate data; however, based on mechanism of action, there is potential for fetal harm, particularly during organogenesis (first trimester). Avoid use in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Acetaminophen has been associated with cases of acute liver failure, sometimes resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed the maximum daily dose (4 grams/day).
| Serious Effects |
["Hypersensitivity to acetaminophen or any component of the formulation","Severe hepatic impairment or active liver disease"]
| Precautions | ["Hepatotoxicity: Risk of acute liver failure with doses exceeding 4g/day, in patients with pre-existing liver disease, or with chronic alcohol use.","Serious skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis can occur at any dose.","Hypersensitivity reactions: Anaphylaxis and angioedema."] |
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| Fetal Monitoring | Monitor complete blood counts regularly due to risk of cytopenias. Assess hepatic and renal function. In pregnancy, perform fetal ultrasound monitoring for growth and anatomy if exposure occurs. Monitor for signs of infection or bleeding. |
| Fertility Effects | Animal studies indicate potential impairment of male and female fertility based on effects on reproductive organs at clinically relevant exposures. No human data; advise patients regarding potential risks to fertility. |